miRNA nanoencapsulation to regulate the programming of the blood-brain barrier permeability by hipoxia.

Central nervous system (CNS)-related diseases are difficult to treat as most therapeutic agents they cannot reach the brain tissue, mainly due to the blood-brain barrier (BBB), arguably the tightest barrier between the human body and cerebral parenchyma, which routinely excludes most xenobiotic therapeutics compounds. The BBB is a multicellular complex that structurally forms the neurovascular unit (NVU) and is organized by neuro-endothelial and glial cells. BBB breakdown and dysfunction from the cerebrovascular cells lead to leakages of systemic components from the blood into the CNS, contributing to neurological deficits. Understanding the molecular mechanisms that regulate BBB permeability and disruption is essential for establishing future therapeutic strategies to restore permeability and improve cerebrovascular health. MicroRNAs (miRNAs), a type of small noncoding RNAs, are emerging as an important regulator of BBB integrity by modulating gene expression by targeting mRNA transcripts. miRNAs is implicated in the development and progression of various illnesses. Conversely, nanoparticle carriers offer unprecedented opportunities for cell-specific controlled delivery of miRNAs for therapeutic purposes. In this sense, we present in this graphical review critical evidence in the regulation of cell junction expression mediated by miRNAs induced by hypoxia and for the use of nanoparticles for the delivery of miRNA-based therapeutics in the treatment of BBB permeability

Methods for Developing a Process Design Space Using Retrospective Data

Prospectively planned designs of experiments (DoEs) offer a valuable approach to preventing collinearity issues that can result in statistical confusion, leading to misinterpretation and reducing the predictability of statistical models. However, it is also possible to develop models using historical data, provided that certain guidelines are followed to enhance and ensure proper statistical modeling. This article presents a methodology for constructing a design space using process data, while avoiding the common pitfalls associated with retrospective data analysis. For this study, data from a real wet granulation process were collected to pragmatically illustrate all the concepts and methods developed in this article

Pharmacy student's engagement, performance and perceptions in a pilot study of cooperative learning applied to 'introduction to the galenic pharmacy' subject

Introduction to the Galenic Pharmacy (IFG) is a required subject of first-year (2nd semester) of Pharmacy Degree of the University of Barcelona (UB). This subject is very conceptual and descrip tive and contains many terms with their corre sponding definitions. It is considered the basis for the subjects of pharmaceutical technology that are studied in higher courses

Robustness Optimization of an Existing Tablet Coating Process Applying Retrospective Knowledge (rQbD) and Validation

The objective of these studies is to verify and validate the improvement in the inter-tablet coating uniformity for an industrially commercialized coated tablet, without involving changes in the approved registration dossier. Using the CPP (critical process parameters) determined from previous retrospective statistical analysis, the recommended working ranges are identified. Retrospective analysis showed that the design of experiments (DoE) provided an improved process variable configuration. Therefore, it is decided to study two critical parameters: Product temperature and drum speed, with an additional 22 experimental design. The quality results of the samples analyzed show that the aesthetic defects of the batches made with the new working ranges have been reduced. These results have also been corroborated with the 42 industrial batches manufactured with the new ranges. With the optimized parameters, tablets have been coated and the suitability of the model determined. The results demonstrated the overall reliability and effectiveness of the proposed Quality by Design approach and provides a useful tool to help optimize the industrial coating process. This study confirms that it is possible to optimize and validate the manufacturing process of an existing commercial product by means of a DoE with retrospective data. Therefore, no variation in the dossier is required

Pellets and gummies: seeking a 3D printed gastro-resistant omeprazole dosage for paediatric administration

The production of 3D printed pharmaceuticals has thrived in recent years, as it allows the generation of cus-tomised medications in small batches. This is particularly helpful for patients who need specific doses or for-mulations, such as children. Compounding pharmacies seek alternatives to conventional solid oral doses, opting for oral liquid formulations. However, ensuring quality and stability, especially for pH-sensitive APIs like omeprazole, remains a challenge. This paper presents the application of semi-solid extrusion 3D printing tech-nology to develop patient-tailored medicinal gummies, with an eye-catching appearances, serving as an inno-vative omeprazole pharmaceutical form for paediatric use. The study compares 3D printing hydrogels with dissolved omeprazole to hydrogels loaded with gastro-resistant omeprazole pellets, a ground-breaking approach.. Gastro-resistance and dissolution profiles were studied using different methods for better comparison and to emphasize the significance of the assay's methodology. Both developed formulas exhibit proper rheology, good printability, and meet content and mass uniformity standards. However, the high gastro-resistance and suitable release profile of 3D printed chewable semi-solid doses with enteric pellets highlight this as an effective strategy to address the challenge of paediatric medication

Excipients in the Paediatric Population: A Review

This theoretical study seeks to critically review the use of excipients in the paediatric population. This study is based on the rules and recommendations of European and American drug regulatory agencies. On the one hand, this review describes the most frequent excipients used in paediatric medicine formulations, identifying the compounds that scientific literature has marked as potentially harmful regarding the side effects generated after exposure. On the other hand, this review also highlights the importance of carrying out safety -checks on the excipients, which, in most cases, are linked to toxicity studies. An excipient in the compilation of paediatric population databases is expected to target safety and toxicity, as in the STEP database. Finally, a promising pharmaceutical form for child population, ODT (Orally Disintegrating Tablets), will be studied

Palatability and stability studies to optimize a carvedilol oral liquid formulation for pediatric use

Carvedilol (CARV) is a blocker of α- and β- adrenergic receptors, used as an “off-label” treatment for cardiovascular diseases in pediatrics. Currently, there is no marketed pediatric-appropriate CARV liquid formulation, so its development is necessary. Palatability (appreciation of smell, taste, and aftertaste) is a key aspect to be considered during the development of pediatric formulations since only formulations with good palatability also have adequate acceptability in this population. Consequently, the aim of this research was to assess the palatability and acceptability of different CARV formulations using an in vivo taste assessment (ID Number PR103/22) in order to select the highest palatability-rated CARV formulation. The preparation of CARV formulations was based on a reference 1 mg/mL CARV solution, which contains malic acid as a solubilizing agent. Subsequently, sucralose and flavoring agents were added and mixed until complete dissolution to the corresponding formulations. Adult volunteers participated in this study and evaluated the taste and odor of various CARV formulations through a questionnaire and a sensory test. The mean palatability score, measured on a 10-point scale, increased from 1.60 for the unflavored control to 7.65 for the highest-rated flavored formulation. Moreover, the bitterness of the optimized CARV formulation was reduced from 66.67% to 17.86%, and the taste pleasantness was increased from 25/100 to 73/100. This optimized CARV formulation contains a sweetening agent, sucralose, in addition to two flavoring agents at appropriate concentrations for pediatrics. Furthermore, the physicochemical and microbiological stability of the optimized CARV formulation were evaluated for 6 months at 25, 30, and 40 °C, in addition to in-use stability for 15 days at 25 °C, whose results were confirmed. Thus, we successfully developed a palatable CARV liquid solution that contains excipients appropriate for pediatrics and is stable under the studied conditions.</span

Isotretinoína para el tratamiento del acné

Se efectúa una revisión de las características fisicoquímicas, farmacológicas, toxicológicas y farmacocinéticas de la isotretinoína, retinoide utilizado en el tratamiento de algunos tipos de acné. También se abordan las ventajas e inconvenientes de su uso en terapéutica, además de posibles precauciones, controversias y contraindicaciones de la misma

Development of a Standardized Method for Measuring Bioadhesion and Mucoadhesion That Is Applicable to Various Pharmaceutical Dosage Forms

Although some methods for measuring bioadhesion/mucoadhesion have been proposed, a standardized method is not yet available. This is expected to hinder systematic comparisons of results across studies. This study aimed to design a single/systematic in vitro method for measuring bioadhesion/mucoadhesion that is applicable to various pharmaceutical dosage forms. To this end, we measured the peak force and work of adhesion of minitablets, pellets, and a bioadhesive emulsion using a texture analyzer. Porcine tissue was used to simulate human stomach/skin conditions. The results of these formulations were then compared to those for formulations without the bioadhesive product. We conducted a case study to assess the stability of a bioadhesive emulsion. The results for the two parameters assessed were contact time = 60 s and contact force = 0.5 N at a detachment speed of 0.1 mm/s. Significant differences were observed between the bioadhesive and control formulations, thus demonstrating the adhesive capacity of the bioadhesive formulations. In this way, a systematic method for assessing the bioadhesive capacity of pharmaceutical dosage forms was developed. The method proposed here may enable comparisons of results across studies, i.e., results obtained using the same and different pharmaceutical formulations (in terms of their bioadhesion/mucoadhesion capacity). This method may also facilitate the selection of potentially suitable formulations and adhesive products (in terms of bioadhesive properties)

Development of a Carvedilol oral liquid formulation for paediatric use

Carvedilol (CARV) is an 'off-label' β-blocker drug to treat cardiovascular diseases in children. Since CARV is nearly insoluble in water, only CARV solid forms are commercialized. Usually, CARV tablets are manipulated to prepare an extemporaneous liquid formulation for children in hospitals. We studied CARV to improve its aqueous solubility and develop an oral solution. In this study, we assessed the solubility and preliminary stability of CARV in different pH media. Using malic acid as a solubility enhancer had satisfactory results. We studied the chemical, physical, and microbiological stability of 1 mg/mL CARV-malic acid solution. A design of experiment (DoE) was used to optimize the CARV solution's preparation parameters. A 1 mg/mL CARV solution containing malic acid was stable for up to 12 months at 25 °C and 30 °C and 6 months at 40 °C. An equation associating malic acid with CARV concentrations was obtained using DoE. Microbiological data showed that the use of methylparaben was not necessary for this period of time. We successfully developed an aqueous CARV solution suitable for paediatrics and proven to be stable over a 12-month period